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Opioids use with inpatients (Proceedings)

Opioids are commonly used in veterinary medicine for their analgesic, sedative, and anti-diarrheal properties. Opioids are also effective antitussive agents and in appropriate doses opioids can provide anxiolytic effects. The analgesic effects of opioids are mediated primarily through activity in the central nervous system (CNS) including the spinal cord and brain. Effects on the gastrointestinal tract (GIT) are primarily local effects and include decreased propulsive contractions, increased segmental contractions, and decreased fluid secretions. Local analgesic effects can also be obtained by direct injection into the synovium. Leukocytes, which have opiate receptors, are also affected by opioids eliciting a range of effects, from immunostimulation to immunosuppression. Studies in humans have demonstrated that withholding opioids in painful patients that are immunocompromised results in worsened immune function.

Mu opioid agonists (morphine, hydromorphone, fentanyl) result in dose-dependent analgesia with larger doses eliciting a greater effect. Mu opioids are effective in treating mild to severe pain. In contrast the partial mu agonist buprenorphine and kappa agonists (butorphanol, nalbuphine) have a ceiling effect, in which a sub-maximum level of analgesia is achieved and additional doses do not result in increased analgesic effects. Partial agonists are effective in treating mild to moderate pain.

Respiratory Effects

Mu opioid agonists produce a dose-dependent respiratory depression in animals while partial mu agonists and kappa agonists produce sub-maximum respiratory depression. In contrast to humans, the respiratory depressant effects of opioids in healthy animals administered clinically recommended doses produce minimal respiratory depression. Doses as high as 50 to 100 times the clinically recommended doses of morphine resulted in severe respiratory depression, but not death in animals. However animals with underlying respiratory disease (bronchitis, asthma, pleural effusion, cor pulmonale, etc.) are at in increased risk for respiratory adverse effects. Animals with head trauma are at an increased risk of cerebral edema when administered opioids as the opioids decrease the animal's response to increasing carbon dioxide levels which can potentially worsen cerebral edema.

Antitussive Effects

Opioids also have antitussive effects which are independent of the respiratory depressant effects. Mu opioid agonists (morphine, hydrocodone, codeine, et al), buprenorphine, and kappa agonists (butorphanol) are effective antitussive agents. Tramadol also has antitussive effects in experimental models, but its effectiveness has not been investigated clinically. The efficacy of tramadol in dogs as an antitussive is expected to be less than other species as the active metabolite is not produced in consistent or high concentrations.

Cardiovascular Effects

Clinically recommended dosages of opioids have minimal effects on the cardiovascular system in animals. The effects of IV morphine at clinically recommended doses on the blood pressure of dogs have been variable ranging from mild decreases to mild increases. Histamine concentrations increase following IV morphine injection, but the clinical relevance appears to be minimal as changes in cardiovascular parameters, including blood pressure, are minimal. In contrast to humans, dogs administered morphine (at higher than recommended doses) had increased coronary vascular resistance and decreased coronary blood flow. Therefore, routine administration of morphine for the treatment of congestive heart failure is not recommended. Opioids result in minimal effects on cardiac output, however decreased heart rate is routinely observed in dogs. Morphine also exerts protective effects towards ventricular tachycardia.

Thermoregulation

Panting commonly occurs in dogs after administration of opioids. Opioids affect the thermoregulatory center in the hypothalamus in dogs which results in a decrease in body temperature due to the increased panting. It is not uncommon for dogs to become hypothermic when administered opioids. In cats, the opposite effect is occasionally seen, in which the body temperature increases, and may occur more frequently with hydromorphone.

Emesis

Opioids (primarily morphine, hydromorphone) can result in emesis following administration to dogs and cats that is thought to be primarily due to stimulation of the chemoreceptor trigger zone (CRTZ). Conversely, some opioids act as antiemetics on the emetic center in the brain. Butorphanol (0.2 - 0.4 mg/kg IV, IM, SC) has been used as an antiemetic in dogs and cats receiving chemotherapy in which the vomiting is not controlled with standard antiemetic drugs. Fentanyl also has demonstrated antiemetic effects. Chronic administration of opioids may result in GI stasis and ileus with vomiting resulting from decreased GIT motility.